AI Article Synopsis
- Major histocompatibility complex (MHC) class I molecules are crucial for presenting peptides to cytotoxic T lymphocytes, primarily derived from cellular protein degradation.
- The process of cross-presentation, particularly in dendritic cells, allows these cells to present peptides from internalized antigens, but the cellular mechanisms are not fully understood.
- This study identifies insulin-regulated aminopeptidase (IRAP) as a key player in cross-presentation, showing that IRAP's trimming of peptides in endosomal compartments is essential for this process, while not affecting the presentation of own cellular peptides.
Article Abstract
Major histocompatibility complex (MHC) class I molecules present peptides, produced through cytosolic proteasomal degradation of cellular proteins, to cytotoxic T lymphocytes. In dendritic cells, the peptides can also be derived from internalized antigens through a process known as cross-presentation. The cellular compartments involved in cross-presentation remain poorly defined. We found a role for peptide trimming by insulin-regulated aminopeptidase (IRAP) in cross-presentation. In human dendritic cells, IRAP was localized to a Rab14+ endosomal storage compartment in which it interacted with MHC class I molecules. IRAP deficiency compromised cross-presentation in vitro and in vivo but did not affect endogenous presentation. We propose the existence of two pathways for proteasome-dependent cross-presentation in which final peptide trimming involves IRAP in endosomes and involves the related aminopeptidases in the endoplasmic reticulum.
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| http://dx.doi.org/10.1126/science.1172845 | DOI Listing |
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